tbuckley/cabot-search huggingface dataset:
Low-Dose Empagliflozin as Adjunct to Hybrid Closed-Loop Insulin Therapy in Adults With Suboptimally Controlled Type 1 Diabetes: A Randomized Crossover Controlled Trial
Authors: Melissa-Rosina Pasqua, Adnan Jafar, Alessandra Kobayati, Michael A. Tsoukas, Ahmad Haidar
Journal: Diabetes Care (2022)

OBJECTIVE To assess whether low doses of empagliflozin as adjunct to hybrid closed-loop therapy improve glycemia compared with placebo in adults with type 1 diabetes (T1D) who are not able to achieve targets with the system alone. RESEARCH DESIGN AND METHODS A double-blind crossover randomized controlled trial was performed in adults with suboptimally controlled T1D (HbA1c 7.0–10.5%) who were not able to achieve a target time in range (3.9–10.0 mmol/L) ≥70% after 14 days of hybrid closed-loop therapy. Three 14-day interventions were performed with placebo, 2.5 mg empagliflozin, or 5 mg empagliflozin as adjunct to the McGill artificial pancreas. Participants were assigned at a 1:1:1:1:1:1 ratio with blocked randomization. The primary outcome was time in range (3.9–10.0 mmol/L). Analysis was by intention to treat, and a P value &amp;lt;0.05 was regarded as significant. RESULTS A total of 24 participants completed the study (50% male; age 33 ± 14 years; HbA1c 8.1 ± 0.5%). The time in range was 59.0 ± 9.0% for placebo, 71.6 ± 9.7% for 2.5 mg empagliflozin, and 70.2 ± 8.0% for 5 mg empagliflozin (P &amp;lt; 0.0001 between 2.5 mg empagliflozin and placebo and between 5 mg empagliflozin and placebo). Mean daily capillary ketone levels were not different between arms. There were no serious adverse events or cases of diabetic ketoacidosis or severe hypoglycemia in any intervention. CONCLUSIONS Empagliflozin at 2.5 and 5 mg increased time in range during hybrid closed-loop therapy by 11–13 percentage points compared with placebo in those who otherwise were unable to attain glycemic targets. Future studies are required to assess long-term efficacy and safety.
Accuracy, interpretability and usability study of a wireless self-guided fetal heartbeat monitor compared to cardiotocography
Authors: Paul Porter, Huaqiong Zhou, Brooke Schneider, Jennifer Choveaux, Natasha Bear, Phillip Della, Kym Jones
Journal: npj Digital Medicine (2022)

Fetal Cardiography is usually performed using in-hospital Cardiotocographic (CTG) devices to assess fetal wellbeing. New technologies may permit home-based, self-administered examinations. We compared the accuracy, clinical interpretability, and user experience of a patient-administered, wireless, fetal heartbeat monitor (HBM) designed for home use, to CTG. Initially, participants had paired HBM and CTG examinations performed in the clinic. Women then used the HBM unsupervised and rated the experience. Sixty-three women had paired clinic-based HBM and CTG recordings, providing 6982 fetal heart rate measures for point-to-point comparison from 126 min of continuous recording. The accuracy of the HBM was excellent, with limits of agreement (95%) for mean fetal heart rate (FHR) between 0.72 and -1.78 beats per minute. The FHR was detected on all occasions and confirmed to be different from the maternal heart rate. Both methods were equally interpretable by Obstetricians, and had similar signal loss ratios. Thirty-four (100%) women successfully detected the FHR and obtained clinically useful cardiographic data using the device at home unsupervised. They achieved the required length of recording required for non-stress test analysis. The monitor ranked in the 96-100th percentile for usability and learnability. The HBM is as accurate as gold-standard CTG, and provides equivalent clinical information enabling use in non-stress test analyses conducted outside of hospitals. It is usable by expectant mothers with minimal training.
Patient and physician factors associated with symptomatic undiagnosed asthma or COPD
Authors: Mathew Cherian, Kate M.A. Magner, G.A. Whitmore, Katherine L. Vandemheen, J. Mark FitzGerald, Celine Bergeron, Louis-Philippe Boulet, Andreanne Cote, Stephen K. Field, Erika Penz, R. Andrew McIvor, Catherine Lemière, Samir Gupta, Irvin Mayers, Mohit Bhutani, Paul Hernandez, M. Diane Lougheed, Christopher J. Licskai, Tanweer Azher, Martha Ainslie, Nicole Ezer, Sunita Mulpuru, Shawn D. Aaron
Journal: European Respiratory Journal (2022)

It remains unclear why some symptomatic individuals with asthma or COPD remain undiagnosed. Here, we compare patient and physician characteristics between symptomatic individuals with obstructive lung disease (OLD) who are undiagnosed and individuals with physician-diagnosed OLD.Using random-digit dialling and population-based case finding, we recruited 451 participants with symptomatic undiagnosed OLD and 205 symptomatic control participants with physician-diagnosed OLD. Data on symptoms, quality of life and healthcare utilisation were analysed. We surveyed family physicians of participants in both groups to elucidate differences in physician practices that could contribute to undiagnosed OLD.Participants with undiagnosed OLD had lower mean pre-bronchodilator forced expiratory volume in 1 s percentage predicted compared with those who were diagnosed (75.2% versus 80.8%; OR 0.975, 95% CI 0.963-0.987). They reported greater psychosocial impacts due to symptoms and worse energy and fatigue than those with diagnosed OLD. Undiagnosed OLD was more common in participants whose family physicians were practising for >15 years and in those whose physicians reported that they were likely to prescribe respiratory medications without doing spirometry. Undiagnosed OLD was more common among participants who had never undergone spirometry (OR 10.83, 95% CI 6.18-18.98) or who were never referred to a specialist (OR 5.92, 95% CI 3.58-9.77). Undiagnosed OLD was less common among participants who had required emergency department care (OR 0.44, 95% CI 0.20-0.97).Individuals with symptomatic undiagnosed OLD have worse pre-bronchodilator lung function and present with greater psychosocial impacts on quality of life compared with their diagnosed counterparts. They were less likely to have received appropriate investigations and specialist referral for their respiratory symptoms.
68Ga-PSMA-11 PET/CT and PET/MRI in Rectal Linitis Plastica Secondary to Prostate Adenocarcinoma
Authors: Qian Zhao, Hui Dong, Aisheng Dong, Changjing Zuo
Journal: Clinical Nuclear Medicine (2022)

Primary or secondary rectal linitis plastica is rare. We describe MRI, 68 Ga-PSMA-11 PET/CT, and PET/MRI findings in a case of rectal linitis plastica secondary to prostate adenocarcinoma. In this case, the rectal linitis plastica was the first manifestation of the prostatic adenocarcinoma, and the rectum was the only metastatic site of the prostate adenocarcinoma. The rectal wall showed circumferential thickening with a concentric ring pattern on MRI, and diffuse intense 68 Ga-PSMA-11 uptake on PET/CT and PET/MRI. Familiarity with the imaging findings of rectal linitis plastica secondary to prostate adenocarcinoma may be helpful for recognition of this rare entity.
Evidence of ACL healing on MRI following ACL rupture treated with rehabilitation alone may be associated with better patient-reported outcomes: a secondary analysis from the KANON trial
Authors: Stephanie Rose Filbay, Frank W Roemer, L Stefan Lohmander, Aleksandra Turkiewicz, Ewa M Roos, Richard Frobell, Martin Englund
Journal: British Journal of Sports Medicine (2022)

Evaluate the natural course of anterior cruciate ligament (ACL) healing on MRI within 5 years of acute ACL rupture and compare 2-year and 5-year outcomes based on healing status and treatment group.Secondary analysis of 120 Knee Anterior Cruciate Ligament Nonsurgical vs Surgical Treatment (KANON) trial participants randomised to rehabilitation and optional delayed ACL reconstruction (ACLR) or early ACLR and rehabilitation. ACL continuity on MRI (Anterior Cruciate Ligament OsteoArthritis Score 0-2) was considered evidence of ACL healing. Outcomes included Knee Injury and Osteoarthritis Outcome Score (KOOS), KOOS patient acceptable symptomatic state (PASS) and treatment failure criteria. Linear mixed models were used to estimate adjusted mean differences (95% CIs) in patient-reported sport and recreational function (KOOS-Sport/Rec) and quality of life (KOOS-QOL) at 2 and 5 years, between participants with MRI evidence of ACL healing and those who had (1) no evidence of ACL healing, (2) delayed ACLR or (3) early ACLR.MRI evidence of ACL healing at 2-year follow-up was observed in 16 of 54 (30%, 95% CI 19 to 43%) participants randomised to optional delayed ACLR. Excluding participants who had delayed ACLR, 16 of 30 (53%, 36-70%) participants managed with rehabilitation-alone displayed MRI evidence of ACL healing. Two-year outcomes were better in the healed ACL group (n=16) compared with the non-healed (n=14) (mean difference (95% CI) KOOS-Sport/Rec: 25.1 (8.6-41.5); KOOS-QOL: 27.5 (13.2-41.8)), delayed ACLR (n=24) (KOOS-Sport/Rec: 24.9 (10.2-39.6); KOOS-QOL: 18.1 (5.4-30.8)) and early ACLR (n=62) (KOOS-Sport/Rec: 17.4 (4.1-30.7); KOOS-QOL: 11.4 (0.0-22.9)) groups. Five-year KOOS-QOL was better in the healed versus non-healed group (25.3 (9.4-41.2)). Of participants with MRI evidence of ACL healing, 63-94% met the PASS criteria for each KOOS subscale, compared with 29-61% in the non-healed or reconstructed groups.MRI appearance of ACL healing after ACL rupture occurred in one in three adults randomised to initial rehabilitation and one in two who did not cross-over to delayed ACLR and was associated with favourable outcomes. The potential for spontaneous healing of the ACL to facilitate better clinical outcomes may be greater than previously considered.ISRCTN84752559.
Effect of oral antimicrobial prophylaxis on surgical site infection after elective colorectal surgery: multicentre, randomised, double blind, placebo controlled trial
Authors: Emmanuel Futier, Samir Jaber, Matthias Garot, Marie Vignaud, Yves Panis, Karem Slim, Jean-Christophe Lucet, Gilles Lebuffe, Alexandre Ouattara, Younes El Amine, Philippe Couderc, Aurélien Dupré, Audrey De Jong, Sigismond Lasocki, Marc Leone, Julien Pottecher, Bruno Pereira, Catherine Paugam-Burtz
Journal: BMJ (2022)

Abstract Objective To investigate whether oral antimicrobial prophylaxis as an adjunct to intravenous antibiotic prophylaxis reduces surgical site infections after elective colorectal surgery. Design Multicentre, randomised, double blind, placebo controlled trial. Setting 11 university and non-university hospitals in France between 25 May 2016 and 8 August 2019. Participants 926 adults scheduled for elective colorectal surgery. Intervention Patients were randomised to receive either a single 1 g dose of ornidazole (n=463) or placebo (n=463) orally 12 hours before surgery, in addition to intravenous antimicrobial prophylaxis before surgical incision. Main outcome measures The primary outcome was the proportion of patients with surgical site infection within 30 days after surgery. Secondary outcomes included individual types of surgical site infections and major postoperative complications (Clavien-Dindo classification grade 3 or higher) within 30 days after surgery. Results Of the 960 patients who were enrolled, 926 (96%) were included in the analysis. The mean age of participants was 63 years and 554 (60%) were men. Surgical site infection within 30 days after surgery occurred in 60 of 463 patients (13%) in the oral prophylaxis group and 100 of 463 (22%) in the placebo group (absolute difference −8.6%, 95% confidence interval −13.5% to −3.8%; relative risk 0.60, 95% confidence interval 0.45 to 0.80). The proportion of patients with deep infections was 4.8% in the oral prophylaxis group and 8.0% in the placebo group (absolute difference −3.2%, 95% confidence interval −6.4% to −0.1%). The proportion of patients with organ space infections was 5.0% in the oral prophylaxis group and 8.4% in the placebo group (absolute difference −3.4%, −6.7% to −0.2%). Major postoperative complications occurred in 9.1% patients in the oral prophylaxis group and 13.6% in the placebo group (absolute difference −4.5%, −8.6% to −0.5%). Conclusion Among adults undergoing elective colorectal surgery, the addition of a single 1 g dose of ornidazole compared with placebo before surgery significantly reduced surgical site infections. Trial registration ClinicalTrials.gov NCT02618720 .
When I use a word . . . . Medical words newly logged in the OED in December 2021
Authors: Jeffrey K Aronson
Journal: BMJ (2022)

<i>Of 709 lexical items in the </i>Oxford English Dictionary<i> newly logged in December 2021, 33 have medical relevance. The term “lateral flow [test]” is newly recorded, but is by no means new to the language, since the first instance dates back to 1989. The hypersensitivity pneumonitis “bird fancier9s lung” is also newly recorded, although dating back to 1966, while other names for types of hypersensitivity pneumonitis or extrinsic allergic alveolitis, apart from farmer’s lung and bagassosis, have not appeared in the dictionary. The newest medical term to enter the dictionary is “gene drive,” which is first recorded from 2004.</i>
Cage-modified hypocrellin against multidrug-resistant Candida spp. with unprecedented activity in light-triggered combinational photodynamic therapy
Authors: Xinyao Liu, Renjie Fang, Rui Feng, Qiaosheng Li, Mingqin Su, Chenglin Hou, Kaiwen Zhuang, Yaling Dai, Nian Lei, Yunbo Jiang, Yuzhou Liu, Yuping Ran
Journal: Drug Resistance Updates (2022)

Infections caused by multidrug-resistant fungi pose a devastating threat to human health worldwide, making new antifungal strategies urgently desired. Antimicrobial photodynamic therapy (aPDT) has gained increasing attention due to its potential in fighting against fungal infection. However, the preparation of highly efficient and water-soluble photosensitizers (PSs) for this purpose remains a challenge. Herein, we present a new strategy to prepare powerful PSs for efficient aPDT by introducing a porous cage compound, which could facilitate the transportation of O2 and reactive oxygen species (ROS). Specifically, the natural PS hypocrellin A (HA) was attached to a novel organic cage compound (covalent organic polyhedra 1 tied, COP1T) with polyethylene glycol (PEG) chains to improve its water solubility. It was found that the resulting COP1T-HA exhibited in vitro antifungal efficiency several folds higher compared to the free HA in fighting against four types of multidrug-resistant fungal planktonic cells and biofilms, including the "super fungus" Candida auris. Interestingly, the red-shift of COP1T-HA adsorption led to the realization of phototheranostic aPDT for cage-modified HA or derivatives. Additionally, COP1T-HA exhibited good biocompatibility, excellent disinfection capacity and wound healing efficiency without obvious toxic effects in vivo of rat model. With further development and optimization, COP1T-HA has great potential to become a new class of antifungal agent to fight against drug-resistant pathogens.
Representational ethical model calibration
Authors: Robert Carruthers, Isabel Straw, James K. Ruffle, Daniel Herron, Amy Nelson, Danilo Bzdok, Delmiro Fernandez-Reyes, Geraint Rees, Parashkev Nachev
Journal: npj Digital Medicine (2022)

Equity is widely held to be fundamental to the ethics of healthcare. In the context of clinical decision-making, it rests on the comparative fidelity of the intelligence - evidence-based or intuitive - guiding the management of each individual patient. Though brought to recent attention by the individuating power of contemporary machine learning, such epistemic equity arises in the context of any decision guidance, whether traditional or innovative. Yet no general framework for its quantification, let alone assurance, currently exists. Here we formulate epistemic equity in terms of model fidelity evaluated over learnt multidimensional representations of identity crafted to maximise the captured diversity of the population, introducing a comprehensive framework for Representational Ethical Model Calibration. We demonstrate the use of the framework on large-scale multimodal data from UK Biobank to derive diverse representations of the population, quantify model performance, and institute responsive remediation. We offer our approach as a principled solution to quantifying and assuring epistemic equity in healthcare, with applications across the research, clinical, and regulatory domains.
Protecting the stars of tomorrow: do international cardiovascular preparticipation screening policies account for the paediatric athlete? A systematic review and quality appraisal
Authors: Nathan R Riding, Dan-Mihai Dorobantu, Craig A Williams, Graham Stuart, Peter Fritsch, Mathew G Wilson, Elias Mossialos, Guido Pieles
Journal: British Journal of Sports Medicine (2022)

Objective (1) Identify and review current policies for the cardiovascular screening of athletes to assess their applicability to the paediatric population and (2) evaluate the quality of these policy documents using the Appraisal of Guidelines for Research &amp; Evaluation II (AGREE II) tool. Design Systematic review and quality appraisal of policy documents. Data sources A systematic search of PubMed, MEDLINE, Scopus, Web of Science, SportDiscus and CINAHL. Eligibility criteria for selecting studies An article was included if it was a policy/position statement/guideline/consensus or recommendation paper relating to athletes and cardiovascular preparticipation screening. Results and summary Of the 1630 articles screened, 13 met the inclusion criteria. Relevance to paediatric athletes was found to be high in 3 (23%), moderate in 6 (46%) and low in 4 (31%), and only 2 provide tailored guidance for the athlete aged 12–18 years. A median 5 related citations per policy investigated solely paediatric athletes, with study designs most commonly being retrospective (72%). AGREEII overall quality scores ranged from 25% to 92%, with a median of 75%. The lowest scoring domains were rigour of development; (median 32%) stakeholder involvement (median 47%) and Applicability (median 52%). Conclusion Cardiac screening policies for athletes predominantly focus on adults, with few providing specific recommendations for paediatric athletes. The overall quality of the policies was moderate, with more recent documents scoring higher. Future research is needed in paediatric athletes to inform and develop cardiac screening guidelines, to improve the cardiac care of youth athletes.
The role of dendritic cells in the immunomodulation to implanted biomaterials
Authors: Siyuan Wang, Yanqi Chen, Zhaoting Ling, Jia Li, Jun Hu, Fuming He, Qianming Chen
Journal: International Journal of Oral Science (2022)

Abstract Considering the substantial role played by dendritic cells (DCs) in the immune system to bridge innate and adaptive immunity, studies on DC-mediated immunity toward biomaterials principally center on their adjuvant effects in facilitating the adaptive immunity of codelivered antigens. However, the effect of the intrinsic properties of biomaterials on dendritic cells has not been clarified. Recently, researchers have begun to investigate and found that biomaterials that are nonadjuvant could also regulate the immune function of DCs and thus affect subsequent tissue regeneration. In the case of proteins adsorbed onto biomaterial surfaces, their intrinsic properties can direct their orientation and conformation, forming “biomaterial-associated molecular patterns (BAMPs)”. Thus, in this review, we focused on the intrinsic physiochemical properties of biomaterials in the absence of antigens that affect DC immune function and summarized the underlying signaling pathways. Moreover, we preliminarily clarified the specific composition of BAMPs and the interplay between some key molecules and DCs, such as heat shock proteins (HSPs) and high mobility group box 1 (HMGB1). This review provides a new direction for future biomaterial design, through which modulation of host immune responses is applicable to tissue engineering and immunotherapy.
Death and End-of-Life Care in Emergency Departments in the US
Authors: Jonathan Elmer, Nancy Mikati, Robert M. Arnold, David J. Wallace, Clifton W. Callaway
Journal: JAMA Network Open (2022)

There are more than 140 million annual visits to emergency departments (EDs) in the US. The role of EDs in providing care at or near the end of life is not well characterized.To determine the frequency of death in the ED or within 1 month of an ED visit in an all-age, all-payer national database.The retrospective cohort study used patient-level data from the nationally representative Optum clinical electronic health record data set for 2010 to 2020. Data were analyzed from January to March 2022.Age, Charlson Comorbidity Index (CCI), and year of ED encounter.The primary outcome was death in the ED, overall and stratified by age, CCI, or year. A key secondary outcome was death within 1 month of an ED encounter. We extrapolated to make national estimates using US Census and Nationwide Emergency Department Sample data.Among a total of 104 113 518 individual patients with 96 239 939 ED encounters, 205 372 ED deaths were identified in Optum, for whom median (IQR) age was 72 (53 to >80) years, 114 582 (55.8%) were male, and 152 672 (74.3%) were White. ED death affected 0.20% of overall patients and accounted for 0.21% of ED encounters. An additional 603 273 patients died within 1 month of an ED encounter. Extrapolated nationally, ED deaths accounted for 11.3% of total deaths from 2010 to 2019, and 33.2% of all decedents nationally visited the ED within 1 month of their death. The proportion of total national deaths occurring in the ED decreased by 0.27% annually (P for trend = .003) but the proportion who died within 1 month of an ED visit increased by 1.2% annually (P for trend < .001). Compared with all ED encounters, patients with visits resulting in death were older, more likely to be White, male, and not Hispanic, and had higher CCI. Among ED encounters for patients aged older than 80 years, nearly 1 in 12 died within 1 month.This retrospective cohort study found deaths during or shortly after ED care were common, especially among patients who are older and with chronic comorbidities. EDs must identify patients for whom end-of-life care is necessary or preferred and be equipped to deliver this care excellently.
CROCCP2 acts as a human-specific modifier of cilia dynamics and mTOR signaling to promote expansion of cortical progenitors
Authors: Roxane Van Heurck, Jérôme Bonnefont, Marta Wojno, Ikuo K. Suzuki, Fausto D. Velez-Bravo, Emir Erkol, Dan Truc Nguyen, Adèle Herpoel, Angéline Bilheu, Sofie Beckers, Catherine Ledent, Pierre Vanderhaeghen
Journal: Neuron (2022)

The primary cilium is a central signaling component during embryonic development. Here we focus on CROCCP2, a hominid-specific gene duplicate from ciliary rootlet coiled coil (CROCC), also known as rootletin, that encodes the major component of the ciliary rootlet. We find that CROCCP2 is highly expressed in the human fetal brain and not in other primate species. CROCCP2 gain of function in the mouse embryonic cortex and human cortical cells and organoids results in decreased ciliogenesis and increased cortical progenitor amplification, particularly basal progenitors. CROCCP2 decreases ciliary dynamics by inhibition of the IFT20 ciliary trafficking protein, which then impacts neurogenesis through increased mTOR signaling. Loss of function of CROCCP2 in human cortical cells and organoids leads to increased ciliogenesis, decreased mTOR signaling, and impaired basal progenitor amplification. These data identify CROCCP2 as a human-specific modifier of cortical neurogenesis that acts through modulation of ciliary dynamics and mTOR signaling.